Long COVID and the cardiovascular system – elucidating causes and cellular mechanisms in order to (...), 2022, Gyöngyösi et al

[Wyva]

Full title: Long COVID and the cardiovascular system – elucidating causes and cellular mechanisms in order to develop targeted diagnostic and therapeutic strategies: A joint Scientific Statement of the ESC Working Groups on Cellular Biology of the Heart and Myocardial & Pericardial Diseases

Abstract

Long COVID has become a world-wide, non-communicable epidemic, caused by long-lasting multi-organ symptoms that endure for weeks or months after SARS-CoV-2 infection has already subsided. This scientific document aims to provide insight into the possible causes and therapeutic options available for the cardiovascular manifestations of long COVID.

In addition to chronic fatigue, which is a common symptom of long COVID, patients may present with chest pain, ECG abnormalities, postural orthostatic tachycardia, or newly developed supraventricular or ventricular arrhythmias. Imaging of the heart and vessels has provided evidence of chronic, post-infectious peri-myocarditis with consequent left or right ventricular failure, arterial wall inflammation or micro-thrombosis in certain patient populations.

Better understanding of the underlying cellular and molecular mechanisms of long COVID will aid in the development of effective treatment strategies for its cardiovascular manifestations. A number of mechanisms have been proposed, including those involving direct effects on the myocardium, micro-thrombotic damage to vessels or endothelium, or persistent inflammation. Unfortunately, existing circulating biomarkers, coagulation and inflammatory markers, are not highly predictive for either the presence or outcome of long COVID when measured 3 months after SARS-CoV-2 infection.

Further studies are needed to understand underlying mechanisms, identify specific biomarkers and guide future preventive strategies or treatments to address long COVID and its cardiovascular sequelae.

Open access (in PDF): https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvac115/6649450?login=false

 

[Wyva]

This is a joint scientific statement from the European Society of Cardiology.

Some excerpts, where ME/CFS is mentioned:

Many symptoms are mild, non-specific and reversible, but moderate, severe and persistent symptoms have also been reported, including thromboembolic consequences, lung fibrosis, chronic inflammatory myocarditis, cardiovascular autonomic vegetative dysregulation (eg: Postural Orthostatic Tachycardia Syndrome or POTS), and chronic post-viral fatigue syndrome (similar to myalgic encephalomyelitis/chronic fatigue syndrome, ME/CFS) leading to chronic disability

The majority of long-COVID patients suffer from chronic fatigue syndrome, a disease entity very similar to ME/CFS. ME/CFS has been suggested to be related to mitochondrial dysfunction and oxidative stress, and the same pathomechanism has therefore been suggested for fatigue in long COVID (Table 7). 12

Treatment options:

Symptomatic treatment

To date, no pharmaceutical agents have been shown to ameliorate all symptoms, or improve imaging and biomarker abnormalities caused by long COVID. In most cases, the therapy of cardiac manifestations is limited to symptomatic treatment, for example anti-vasospastic drugs in patients with atypical angina or beta-blockers for palpitations. Medicinal treatment strategies for POTS include alpha-1 agonists, steroids, compression garments, fluid and salt intake, whereas those for CFS include Toll-like receptor-3 agonists, analgesics, and mitochondrial modulators including Coenzyme Q10. Therapy options for mast cell activation syndromes include anti-histamines, mast cell stabilators or leukotriene antagonist.94 Non24 steroidal anti-inflammatory drugs may be used to manage specific symptoms such as fever and pain.

Dietary supplements or other non-specific treatments

Several dietary supplements with putative antioxidant, anti-inflammatory, immunomodulatory, cardio- or neuroprotective effects have been recommended, such as high-dose Vitamin C or different Vitamin complexes, Iron, Selenium, Zinc, etc, beside antihistamines, H2-receptor blockers, or low-dose betablockers.182, 183 Several patients report some symptom improvement, with individual reactions to these substances. Anecdotical case reports have been published on hyperbaric oxygen therapy184, 185 or Aptamer BC007186 though without a strong scientific basis. There are currently more than 300 interventional studies of “long COVID” or “post COVID” registered on clinicaltrials.gov. The NIH has recently provided $470 million to fund the “Researching COVID to Enhance Recovery (RECOVER) Initiative” (https://www.nih.gov/news-events/news-releases/nih-builds large-nationwide-study-population-tens-thousands-support-research-long-term-effects-covid-19).

Clinical implication: There is currently no evidence-based data for therapy of long COVID, and a lack of randomized clinical trials. Until the precise cause of long COVID and its cardiovascular manifestations become clear, it is difficult to predict which interventions are likely to be effective. However, given the increasingly intense investigation in this area, the situation is likely to improve.

Rehabilitation programs

A personalized multi-disciplinary rehabilitation approach involving breathing, mobilisation, “paced” training (pacing) and psychological interventions has improved lung function and physical capacity in post-COVID patients.187, 188 Therefore, light aerobic exercise paced according to individual capacity may be effective in treating post-COVID in some patients. However, certain long-COVID conditions such as POTS or CFS with post-exertional malaise do not always respond favourably to physical rehabilitation.94 It is important to emphasize the role of the patient in developing “coping” strategies to fight against long24 COVID. There are several e-cardiology programs or on-line training available (e.g. brain training, fatigue-training, yoga, breathing-training), and also recommendations for home training for patients with POTS189 and wearable smartwatch measuring heart rate, blood pressure, ECG and some other physiological parameters.38, 190 It is important that patients do regular check-ups and maintain their cardiovascular health.

Clinical implication: Individual rehabilitation programs including “pacing” and “coping”, as well as on-line training programs are important therapeutic strategies for long-COVID patients.

Vaccination

The Office for National Statistics UK study published a 41% decrease in self-reported long-COVID symptoms if the vaccine was applied at least 2 weeks before the infection in more than 1 million infected patients.191 Two doses vaccination before infection with SARS-CoV-2 was also associated with substantial decrease in PASC in a smaller Israel study published in pre-print.192 Vaccination was associated with improved symptoms in 56.7% of patients in a large (n=900 patients) cohort but also in small case series of 163 patients with long COVID even if some patients reported unchanged symptoms.193

Clinical implication: Vaccination prior to COVID-19 infection significantly prevents the occurrence of long COVID after infection, but also reduces long-COVID symptoms if the patient was previously infected. An undoubted advantage of vaccination is the decrease in new infection and alleviation of the disease course of new infections, thereby reducing the incidence and severity of long COVID.

 

[rvallee]

A personalized multi-disciplinary rehabilitation approach involving breathing, mobilisation, “paced” training (pacing)

Clinical implication: Individual rehabilitation programs including “pacing” and “coping”, as well as on-line training programs are important therapeutic strategies for long-COVID patients.

Ignorance is strength. Literally the opposite of rehabilitation and a complete perversion of what pacing means. I'm not even sure what coping is supposed to mean, other than a formal "suck it up, buttercup, no one believes it's that bad". Seriously what even is coping here?

The level of tolerance for performative nonsense, rituals that do nothing, in healthcare is seriously alarming. Exactly how much of medical care is completely useless?

 

[SNT Gatchaman]

Endotheliopathy and coagulation markers remain elevated in a significant proportion of convalescent patients, suggesting that the infection creates a chronic coagulopathy, endotheliitis, or microangiopathy with microthrombosis which may drive myocardial dysfunction, although so far, the effect on heart function appears to be relatively minimal. This condition should be appropriately monitored in the future by studies in larger patient cohorts, taking advantage of advanced imaging systems such as cMRI.

Clinical implication: Micro- and macro-vessel changes are associated with endothelial dysfunction, coagulopathy, and microthrombi, and are likely to be major factors in the persistence of cardiovascular manifestations of long-COVID syndrome.